The goal is to identify genes determining genetic variants of the electroencephalogram (EEG) and evoked responses of the EEG and event- related potentials (ERPs) to identify vulnerability genes for alcoholism and related behaviors with genetic components. This initiative is being pursued by: (1) family transmission and association studies on families identified by a population-based survey for probands with EEG and ERP variants; and (2) a genetic linkage study to map the genes determining the variants. In the genetic epidemiological study, the low voltage alpha (LVA), EEG variant was confirmed to be transmitted in autosomal dominant fashion at least in some families. High and low P300 ERP families have also been identified. Alcoholism and anxiety disorders were more frequent in individuals with the LVA trait, potentially identifying a more homogeneous subgroup of alcoholics with a genetic vulnerability mediated through the anxiety dimension of temperament. Families with the LVA variant, P300 variants, and alcoholism have been collected and families are being analyzed for genetic linkage to dispersed and candidate gene DNA markers. The potassium channel gene DRK1 is located on chromosome 20q where a locus for the low voltage alpha (LVA) EEG trait was previously identified in approximately one-third of families with LVA. LVA is positively associated with alcoholism (see above). Using direct gene analysis methods described in Z01 AA 00290-05 LNG, a nonconservative amino acid substitution was identified in DRF1 by Drs. S. Michelini and C. Mazzanti. However, this polymorphism is not associated with this quantitative EEG phenotype.